Review of Photodynamic Therapy as an Alternative to Isotretinoin for Acne Treatment

Heather N. Valasek
University of Lynchburg,valaseh256@lynchburg.edu

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Recommended Citation
Valasek HN. Review of Photodynamic Therapy as an Alternative to Isotretinoin for Acne Treatment.
University of Lynchburg DMSc Doctoral Project Assignment Repository. 2025; 7(2).

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Heather Valasek PA-C, Diplomate Fellow SDPA

School of Medicine and Health Sciences

Doctor of Medical Science Program

University of Lynchburg

Dr. Debra S. Munsell, DHSc, PA-C, DFAAPA

PA966B: Doctoral Project

03/04/2025

INTRODUCTION

In a review of the current literature, the following articles helped establish the legitimacy of ALA-PDT treatment for moderate to severe acne. Acne is a prevalent skin condition seen and treated globally by medical practitioners. Approximately 20% of all acne sufferers have moderate to severe acne. ¹ Use of modern devices to effectively treat this disease process in a non-systemic way is possible. Yet, the U.S. still heavily relies on prescribing a knowingly hazardous oral medication called ISO. If one of these non-invasive treatment options is as effective as ISO, then progress should be made toward adopting it as the new standard so that patients can be treated as harmlessly as possible. For nearly forty years, U.S. providers have considered oral isotretinoin (ISO) the gold standard for patients who have scarring, recalcitrant, or moderate to severe acne. ² ISO drug labeling includes a black box warning for teratogenicity and a warning for side effects such as psychosis, depression, pseudotumor cerebri, pancreatitis, hearing impairment, visual impairment, hepatotoxicity, decreased bone mineral density, and inflammatory bowel disease, to name a few. Before treatment can be initiated, ISO requires a waiting period of one month for patients who can become pregnant to have two negative pregnancy tests. Pregnancy tests must be performed and recorded each month before writing another month’s prescription. These patients must agree to remain on two forms of birth control during treatment and for a month after discontinuing ISO. Also required is regular lab work monitoring by the prescriber and monthly questions that must be answered by both the provider and the patient through an online portal called Ipledge.

In contrast to the United States, countries in Europe and Asia have been using photodynamic therapy (PDT) treatments with the topical application of 5-aminolevulinic acid (ALA) safely and effectively. In the clinical setting, ALA gel or solution is applied topically to a patient’s clean, dry skin. It absorbs into the treated area for an incubation period, typically 90 minutes for facial acne. Then, the patient is placed under a medical grade blue, red, or mixed blue/red LED light source for ten to twenty minutes, depending on the type of light source and the amount of energy it emits. ³ The ALA is a photosensitizing agent absorbed by abnormal cells which are then activated when interacting with the light source creating the treatment option known as ALA- PDT⁴. This leads to significant uptake at the gene expression level and has been scientifically shown to halt the chronic inflammation cycle of acne. ⁵

A literature review was done to determine whether this non-pharmacotherapy treatment has been sufficiently studied and can be deemed a viable alternative treatment in inflammatory, scarring, or recalcitrant moderate to severe acne cases. Those studies that contributed to an understanding of the safety and efficacy of ALA-PDT are included in this review. The purpose is to educate providers on an alternative treatment option to the commonly prescribed ISO in an attempt to reconsider which therapy option is best for the overall health and well-being of each patient.

DISCUSSION

Methods

PUBMED searches were performed using search terms and restricted to only randomized controlled trials (RCTs) within the past five years. The keywords “isotretinoin” and “photodynamic therapy” were initially searched with Boolean “AND” to ensure that enough research on PDT in acne treatment exists in the literature to then compare it to ISO treatment. To get more results, a clinical query was done searching the keywords “acne treatment” and ‘photodynamic therapy” and filtering for therapy type using a narrow search.

Two PubMed results came from searching “isotretinoin” AND “photodynamic therapy”. One was excluded due to the study of a combination therapy of PDT with isotretinoin. The other was included. Clicking on “similar articles” while on its page produced another appropriate study. Although it was written in 2009, the date of this systematic review solidifies that PDT has been used safely and effectively for over fifteen years in China for the treatment of moderate to severe acne, therefore, it was included for discussion.

The clinical query generated sixty articles. Most were eliminated for comparing PDT with another treatment of no particular interest or due to the study being published more than five years ago. However, one relevant and current article comparing various non-invasive treatments for acne was included as it showed PDT being the superior treatment compared to all the other lasers and devices studied. Another was included due to it looking at optimizing PDT protocols for acne treatment and reduction of side effects while maintaining desirable outcomes. After inspecting the 63 PubMed-generated articles, 10 were considered instrumental for this literature review.

Results

Zhang et al. ⁶published a multicenter randomized clinical trial comparing a 6-month course of low dose ISO and 5 weekly treatments of ALA-PDT in patients with moderate to severe acne. The researchers studied efficacy showing that getting to an improvement of half as many lesions took far less time for the PDT patients. The effective rate when assessed at the one-month mark was much higher in the PDT group than in the ISO group. ⁶ The study also found that more than 70% of the ISO group had systemic side effects, whereas the PDT group had no systemic side effects. ⁶ The study only had 152 patients. However, it was clearly concluded that the PDT treatment was shorter, as efficacious or more so than ISO, treatment with PDT worked more quickly, and PDT offered patients better full body health during and after treatment. ⁶

Although PDT treatment side effects are only experienced within the skin, Wojewoda et al. wanted to reduce these side effects by optimizing their treatment protocol through a thirty-three patient, double blind, randomized controlled trial. ⁷ They found that they could reduce the energy emitted from the red light device from 37 Joules (J) to 20J. This increases tolerability and reduces the pain the patient experiences due to treatment while still maintaining good results.

Another conclusion from this study is that there is still no unanimity among providers for an ALA-PDT acne treatment protocol. This lack of consensus contributes to inhibiting ALA-PDT from becoming a more suggested treatment option. ⁷

According to M.N. Landis, ISO provides unparalleled results for acne treatment. ⁸ However, this literature review found studies on other treatment modalities, such as PDT, that disproved that statement. Landis’s guidelines state that rather than the typical 120-150mg/kg dose, treatment protocols for ISO are to achieve clearance of acne then continue treatment for one full month of being clear. ⁸ This could shorten the length of treatment for some patients, though it does not prevent adverse effects. Labs are still reviewed to ensure that a patient has not become pregnant and to monitor for common side effects such as hepatotoxicity and hypertriglyceridemia. ⁸

The most informative article for PDT to treat acne might be through a systematic review of PubMed, Cochrane, and CKNI by Zheng et al. ⁹ The review studied 14 RCTS and 492 patients in total. ⁹ Zheng et al. discovered that PDT is indeed a good treatment option for acne with tolerable and short-lived side effects. ⁹ Researchers gleaned that the ALA with red light PDT was the overall best in the treatment of acne amongst all the other PDT options. ⁹ The clinical outcomes demonstrated that ALA-PDT invokes less health risk for the patient during and after treatment with comparable outcomes in reduction of acne and longevity of results. ⁹

Patient Need

This research was carried out to find an alternative solution for those patients who are contraindicated to ISO, apprehensive to take ISO due to its potential adverse side effects, patients who will not adhere to daily topical or oral regimens, and those minor patients whose parents will not allow their child with acne to take ISO. Scenarios such as these need to be approached with evidence-based medicine.

Patient Experience

ALA-PDT offers an alternative option to patients who are more sensitive to, or anxious about, oral medications such as ISO due to its side effects profile. A patient undergoing ISO treatment can experience internal, adverse side effects during the months-long treatment course as well as for many years thereafter. How much potential harm ISO can produce is difficult to ascertain, as most studies do not follow the patient experience years out.

The studies reviewed proved that the ALA-PDT option does not produce side effects beyond the skin. Thus, it is a much more tolerable experience even at the highest reported energy level used for PDT at 37J. However, ALA-PDT treatment can be an uncomfortable experience for patients. Because of this, one study had patients undergo more frequent treatments at a lower energy level so that tolerability was maintained throughout the entire treatment plan. This was accomplished with five weekly treatments of ALA and PDT at 20J. ⁷

Advantages of ALA-PDT

Side effects are temporary, limited to the skin, and not systemic. The duration of treatment with ALA-PDT is much shorter than a typical ISO course, often 6 weeks compared to 6 months, respectively. No daily tasks for the patient to perform. Two forms of birth control are not required as they are for ISO therapy. No lab work is necessary. There is no waiting period to begin treatment while the acne is uncontrolled or getting worse. Typically, a patient achieves similar results to that of ISO more quickly and without harming the patient or a patient’s fetus.

Considerations and Limitations

Economic considerations and tolerability for all Fitzpatrick skin types need further study.

Future Trajectory

ALA-PDT is FDA-approved and currently being offered in the U.S. to treat actinic keratoses (AKs). ¹⁰ Although acne is not yet an FDA-approved indication for ALA-PDT treatment, commercial ALA manufacturers are currently presenting their cases. According to clinicaltrials.gov, brand name ALA, Ameluz, and the light source, Rhodo LED, are currently recruiting adults with moderate to severe acne for a study to evaluate the safety and efficacy. With RCTs guiding us, standardized treatment protocols are being set up by researchers and providers alike. The groundwork has begun for ALA-PDT to become FDA-approved soon. Soon after could be a widespread adoption by U.S. providers and insurance coverage shortly thereafter.

CONCLUSION

This literature review aims to provide sufficient evidence that ALA-PDT is an evidence-based option to consider rather than ISO therapy for many patients with moderate to severe acne.

Technology for the treatment of acne has advanced much in the past 40 years, yet the mainstay of treatment during this period in the U.S. continues to be ISO, despite a known risk profile. Access to a high-quality PDT light source as well as the cost of commercial ALA are two potential obstacles to patients receiving this acne treatment. Because of its indication for AKs, many providers already have the necessary resources to offer ALA-PDT treatment ‘off-label’ to patients with acne. Protocols of ALA-PDT should be developed from the existing studies and agreed upon universally. ALA-PDT treatment for acne rather than ISO would get rid of delayed waiting times for pregnancy testing and lab results, eliminate the risk of possible systemic symptoms, often clear the skin more quickly, and prevent internal damage to the patient or a patient’s fetus. The research reveals ALA-PDT for the treatment of specific acne conditions to be safe, effective, long-lasting, and tolerable for most patients. Practitioners can now be well- informed and confident in offering ALA-PDT to appropriate patients who are interested in non- systemic, non-pharmacotherapy treatments for acne.

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